UA73762C2 - Піримідинові сполуки, спосіб їх одержання, фармацевтична композиція та їх використання - Google Patents
Піримідинові сполуки, спосіб їх одержання, фармацевтична композиція та їх використання Download PDFInfo
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- UA73762C2 UA73762C2 UA2002097389A UA2002097389A UA73762C2 UA 73762 C2 UA73762 C2 UA 73762C2 UA 2002097389 A UA2002097389 A UA 2002097389A UA 2002097389 A UA2002097389 A UA 2002097389A UA 73762 C2 UA73762 C2 UA 73762C2
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- ethyl
- prom
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- spol
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- 238000002360 preparation method Methods 0.000 title description 7
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- QULYNCCPRWKEMF-UHFFFAOYSA-N parachlorobenzotrifluoride Chemical compound FC(F)(F)C1=CC=C(Cl)C=C1 QULYNCCPRWKEMF-UHFFFAOYSA-N 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
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- QYPDJIDQEZDFLS-UHFFFAOYSA-N tert-butyl 2-iodoacetate Chemical compound CC(C)(C)OC(=O)CI QYPDJIDQEZDFLS-UHFFFAOYSA-N 0.000 description 1
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- QERYCTSHXKAMIS-UHFFFAOYSA-M thiophene-2-carboxylate Chemical compound [O-]C(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-M 0.000 description 1
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- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/56—One oxygen atom and one sulfur atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
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| GB0003636A GB0003636D0 (en) | 2000-02-16 | 2000-02-16 | Novel compounds |
| GB0101437A GB0101437D0 (en) | 2001-01-19 | 2001-01-19 | Novel Compounds |
| PCT/EP2001/001515 WO2001060805A1 (en) | 2000-02-16 | 2001-02-13 | Pyrimidine-4-one derivatives as ldl-pla2 inhibitors |
Publications (1)
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Families Citing this family (61)
| Publication number | Priority date | Publication date | Assignee | Title |
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| AU3546601A (en) * | 2000-02-16 | 2001-08-27 | Smithkline Beecham Plc | Pyrimidine-4-one derivatives as LDL-PLA<sub>2</sub> inhibitors |
| GB0024807D0 (en) | 2000-10-10 | 2000-11-22 | Smithkline Beecham Plc | Novel compounds |
| MXPA03003397A (es) * | 2000-10-20 | 2004-06-30 | Biovitrum Ab | N1-(bencensulfonil)indoles sustituidos en las posiciones 2-, 3-, 4-, o 5 y su uso en terapia. |
| GB0119795D0 (en) | 2001-08-14 | 2001-10-03 | Smithkline Beecham Plc | Novel process |
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| GB0127140D0 (en) * | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Novel compounds |
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| GB0127139D0 (en) * | 2001-11-10 | 2002-01-02 | Smithkline Beecham | Novel compounds |
| WO2003057671A1 (fr) * | 2001-12-28 | 2003-07-17 | Takeda Chemical Industries, Ltd. | Compose biaryle et son utilisation |
| US6939863B2 (en) | 2002-01-04 | 2005-09-06 | Wei-Jan Chen | Prevention of atherosclerosis and restenosis |
| GB0208279D0 (en) * | 2002-04-10 | 2002-05-22 | Glaxo Group Ltd | Novel compounds |
| GB0208280D0 (en) * | 2002-04-10 | 2002-05-22 | Glaxo Group Ltd | Novel compounds |
| US20050227974A9 (en) * | 2002-08-01 | 2005-10-13 | Euro-Celtique S.A. | Aminoalkyl-substituted aryl compounds and their use as sodium channel blockers |
| JP4366122B2 (ja) * | 2003-06-24 | 2009-11-18 | 日立オムロンターミナルソリューションズ株式会社 | 紙葉類搬送装置 |
| GB0320522D0 (en) * | 2003-09-02 | 2003-10-01 | Glaxo Group Ltd | Formulation |
| AU2004291262C1 (en) | 2003-11-05 | 2011-08-11 | F. Hoffmann-La Roche Ag | Phenyl derivatives as PPAR agonists |
| US20150017671A1 (en) | 2004-04-16 | 2015-01-15 | Yaping Shou | Methods for detecting lp-pla2 activity and inhibition of lp-pla2 activity |
| JP4812751B2 (ja) | 2004-04-16 | 2011-11-09 | グラクソ グループ リミテッド | Ｌｐ−ＰＬＡ２活性およびＬｐ−ＰＬＡ２活性阻害を検出する方法 |
| TW200608976A (en) | 2004-05-08 | 2006-03-16 | Neurogen Corp | 4,5-disubstituted-2-aryl pyrimidines |
| DE102004061005A1 (de) * | 2004-12-18 | 2006-06-22 | Bayer Healthcare Ag | 3-Cycloalkyl-1,2,4-triazin-5(2H)-one |
| US7705005B2 (en) * | 2006-10-13 | 2010-04-27 | Glaxo Group Limited | Bicyclic heteroaromatic compounds |
| US20080090852A1 (en) * | 2006-10-13 | 2008-04-17 | Colin Andrew Leach | Bicyclic Heteroaromatic Compounds |
| US20080090851A1 (en) * | 2006-10-13 | 2008-04-17 | Colin Andrew Leach | Bicyclic Heteroaromatic Compounds |
| EP2977452A3 (de) | 2007-05-11 | 2016-05-25 | Thomas Jefferson University | Verfahren zur behandlung und vorbeugung von neurodegenerativen erkrankungen und störungen |
| US8962633B2 (en) | 2007-05-11 | 2015-02-24 | Thomas Jefferson University | Methods of treatment and prevention of metabolic bone diseases and disorders |
| MX2009012197A (es) | 2007-05-11 | 2010-01-15 | Univ Pennsylvania | Metodos para tratamiento de ulceras en la piel. |
| US8637524B2 (en) | 2009-07-28 | 2014-01-28 | Auspex Pharmaceuticals, Inc | Pyrimidinone inhibitors of lipoprotein-associated phospholipase A2 |
| TW201209043A (en) * | 2010-05-17 | 2012-03-01 | Glaxo Group Ltd | Novel processes |
| US9011821B2 (en) | 2010-06-18 | 2015-04-21 | Whitehead Institute For Biomedical Research | PLA2G16 as a target for antiviral compounds |
| MX2013006342A (es) * | 2010-12-06 | 2013-08-26 | Glaxo Group Ltd | Compuestos de pirimidinona para usarse en el tratamiento de enfermedades o afecciones mediadas por fosfolipasa asociada con lipoproteinas a2 (lp-pla2). |
| CN104478812A (zh) * | 2010-12-06 | 2015-04-01 | 葛兰素集团有限公司 | 用于治疗由Lp-PLA2介导的疾病或病症的嘧啶酮化合物 |
| JP2013544854A (ja) * | 2010-12-06 | 2013-12-19 | グラクソ グループ リミテッド | 化合物 |
| US20130267544A1 (en) | 2010-12-17 | 2013-10-10 | Peter Adamson | Use of LP-PLA2 Inhibitors in the Treatment and Prevention of Eye Diseases |
| CN102643269B (zh) * | 2011-02-21 | 2014-07-23 | 天津药物研究院 | 一类含吡唑结构的磷脂酶a2抑制剂及用途 |
| CN103476414B (zh) * | 2011-03-16 | 2015-07-08 | 中国科学院上海药物研究所 | 季铵盐类化合物、其制备方法、药物组合物及用途 |
| WO2012129792A1 (zh) * | 2011-03-30 | 2012-10-04 | 中国科学院上海药物研究所 | 嘧啶酮类化合物、其制备方法及药物组合物和用途 |
| US20140171431A1 (en) * | 2011-06-27 | 2014-06-19 | Jianhua Shen | Azole heterocyclic compound, preparation method, pharmaceutical composition and use |
| CN103827116B (zh) * | 2011-07-27 | 2016-08-31 | 葛兰素集团有限公司 | 用作LP-PLA2抑制剂的2,3-二氢咪唑并[1,2-c]嘧啶-5(1H)-酮化合物 |
| WO2013013503A1 (en) | 2011-07-27 | 2013-01-31 | Glaxo Group Limited | 2,3-dihydroimidazo[1,2-c] pyrimidin-5(1h)-one compounds use as lp-pla2 inhibitors |
| EP2736908A1 (de) | 2011-07-27 | 2014-06-04 | Glaxo Group Limited | Bicyclische pyrimidonverbindungen |
| CN105008365B (zh) | 2013-01-25 | 2017-03-15 | 葛兰素史密斯克莱知识产权发展有限公司 | 化合物 |
| SG11201505520WA (en) | 2013-01-25 | 2015-08-28 | Glaxosmithkline Ip Dev Ltd | 2,3-DIHYDROIMIDAZOL[1,2-C]PYRIMIDIN-5(1H)-ONE BASED LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 (LP-PLA<sb>2</sb>) INHIBITORS |
| EP2948456A4 (de) | 2013-01-25 | 2016-09-14 | Glaxosmithkline Ip Dev Ltd | Bicyclische pyrimidonverbindungen als lp-pla2-hemmer |
| US20140283157A1 (en) | 2013-03-15 | 2014-09-18 | Diadexus, Inc. | Lipoprotein-associated phospholipase a2 antibody compositions and methods of use |
| WO2015087239A1 (en) | 2013-12-11 | 2015-06-18 | Ranbaxy Laboratories Limited | Processes for the preparation of darapladib and its intermediates |
| WO2015092687A2 (en) | 2013-12-17 | 2015-06-25 | Ranbaxy Laboratories Limited | Process for the purification of darapladib |
| WO2015114479A1 (en) | 2014-01-28 | 2015-08-06 | Ranbaxy Laboratories Limited | Crystalline forms of darapladib oxalate, adipate, succinate, phosphate, sulphate, fumaratetartrate, nitrate and borate |
| WO2016012917A1 (en) | 2014-07-22 | 2016-01-28 | Glaxosmithkline Intellectual Property Development Limited | 1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2 |
| WO2016012916A1 (en) | 2014-07-22 | 2016-01-28 | Glaxosmithkline Intellectual Property Development Limited | 1,2,3,5-tetrahydroimidazo[1,2-c]pyrimidine derivatives useful in the treatment of diseases and disorders mediated by lp-pla2 |
| DK3186242T3 (da) | 2014-08-29 | 2021-12-20 | Tes Pharma S R L | Alfa-amino-beta-carboxymuconsyre-semialdehyd-decarboxylasehæmmere |
| CN105777653A (zh) * | 2014-12-26 | 2016-07-20 | 中国科学院上海药物研究所 | 用作Lp-PLA2抑制剂的嘧啶酮类化合物及其药物组合物 |
| CN104840963B (zh) * | 2015-05-26 | 2018-02-16 | 河北东康生物科技有限公司 | 含脂蛋白相关性磷脂酶a2抑制剂的药物组合物及应用 |
| WO2016198691A1 (en) * | 2015-06-11 | 2016-12-15 | Basilea Pharmaceutica Ag | Efflux-pump inhibitors and therapeutic uses thereof |
| PE20181487A1 (es) * | 2015-12-16 | 2018-09-18 | Bristol Myers Squibb Co | Heteroarilhidroxipirimidinonas como agonistas del receptor de apelina (apj) |
| US10878307B2 (en) * | 2016-12-23 | 2020-12-29 | Microsoft Technology Licensing, Llc | EQ-digital conversation assistant |
| EP3687980B1 (de) * | 2017-09-26 | 2022-01-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Radioaktiv markiertes darapladib, analoga davon und deren verwendung als bildgebungsverbindungen |
| CN110746445B (zh) * | 2019-10-16 | 2021-03-16 | 深圳海关食品检验检疫技术中心 | 一种头孢哌酮氘代内标物的制备方法 |
| AU2020379796C1 (en) | 2019-11-09 | 2024-05-02 | Shanghai SIMR Biotechnology Co., Ltd | Tricyclic dihydroimidazopyrimidone derivative, preparation method therefor, pharmaceutical composition and use thereof |
| CN115304620A (zh) | 2021-05-07 | 2022-11-08 | 上海赛默罗生物科技有限公司 | 嘧啶酮衍生物、其制备方法、药物组合物和用途 |
| EP4257133A1 (de) | 2022-04-05 | 2023-10-11 | Institut Pasteur | Oxo-azaheterozyklische derivate zur verwendung bei der behandlung von malaria |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69423436T2 (de) | 1993-06-25 | 2000-09-07 | Smithkline Beecham P.L.C., Brentford | An lipoprotein gebundene phospholipase a2, inhibitoren davon und deren verwendung für diagnose und therapie |
| ATE201905T1 (de) * | 1993-10-06 | 2001-06-15 | Icos Corp | Acethylhydrolase des plättchen aktivierenden faktors |
| GB9421816D0 (en) | 1994-10-29 | 1994-12-14 | Smithkline Beecham Plc | Novel compounds |
| CA2208530A1 (en) | 1994-12-22 | 1996-06-27 | Smithkline Beecham P.L.C. | Substituted azetidin-2-ones for treatment of atherosclerosis |
| CH690264A5 (fr) | 1995-06-30 | 2000-06-30 | Symphar Sa | Dérivés aminophosphonates substitués, leur procédé de préparation et leur utilisation pour la préparation de compositions pharmaceutiques. |
| KR19990028630A (ko) | 1995-07-01 | 1999-04-15 | 데이비드 로버츠 | 아테롬성 동맥경화증을 치료하기 위한 아제티디논 유도체 |
| WO1997012963A2 (en) | 1995-09-29 | 1997-04-10 | Smithkline Beecham Plc | A paf-acetylhydrolase and use in therapy |
| JP2000505063A (ja) | 1995-12-08 | 2000-04-25 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | アテローム性動脈硬化症の治療のためのアゼチジノン化合物 |
| JP2000502079A (ja) | 1995-12-08 | 2000-02-22 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | アテローム性動脈硬化症の治療のための単環β―ラクタム誘導体 |
| GB9608649D0 (en) | 1996-04-26 | 1996-07-03 | Smithkline Beecham Plc | Novel compounds |
| HUP9901359A3 (en) | 1996-04-26 | 2000-03-28 | Smithkline Beecham Plc | Azetidinone derivatives for the treatment of atherosclerosis, process for their producing and pharmaceutical compositions containing them |
| GB9626536D0 (en) | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
| GB9626615D0 (en) | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
| GB9626616D0 (en) | 1996-12-20 | 1997-02-05 | Symphar Sa | Novel compounds |
| AU1157599A (en) * | 1997-11-06 | 1999-05-31 | Smithkline Beecham Plc | Pyrimidinone compounds and pharmaceutical compositions containing them |
| EP1105377B1 (de) * | 1998-08-21 | 2003-10-08 | SmithKline Beecham plc | Pyrimidinonderivate zur behandlung von atheroscleros |
| AU766003B2 (en) * | 1999-05-01 | 2003-10-09 | Smithkline Beecham Plc | Pyrimidinone compounds |
| GB9910079D0 (en) | 1999-05-01 | 1999-06-30 | Smithkline Beecham Plc | Novel compounds |
| GB9910378D0 (en) | 1999-05-05 | 1999-06-30 | Smithkline Beecham Plc | Novel compounds |
| AU3546601A (en) * | 2000-02-16 | 2001-08-27 | Smithkline Beecham Plc | Pyrimidine-4-one derivatives as LDL-PLA<sub>2</sub> inhibitors |
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| GB0024808D0 (en) * | 2000-10-10 | 2000-11-22 | Smithkline Beecham Plc | Novel compounds |
-
2001
- 2001-02-13 AU AU3546601A patent/AU3546601A/xx active Pending
- 2001-02-13 PL PL357382A patent/PL209824B1/pl unknown
- 2001-02-13 CZ CZ2002-2768A patent/CZ304450B6/cs not_active IP Right Cessation
- 2001-02-13 AT AT01907522T patent/ATE333446T1/de active
- 2001-02-13 EP EP06075890A patent/EP1686119B1/de not_active Expired - Lifetime
- 2001-02-13 PT PT01907522T patent/PT1263740E/pt unknown
- 2001-02-13 DE DE60139429T patent/DE60139429D1/de not_active Expired - Lifetime
- 2001-02-13 MX MXPA02008062A patent/MXPA02008062A/es active IP Right Grant
- 2001-02-13 BR BRPI0108396-1A patent/BRPI0108396B1/pt not_active IP Right Cessation
- 2001-02-13 KR KR1020027010662A patent/KR100781425B1/ko not_active IP Right Cessation
- 2001-02-13 AU AU2001235466A patent/AU2001235466B2/en not_active Ceased
- 2001-02-13 AT AT06075890T patent/ATE437862T1/de active
- 2001-02-13 SK SK1177-2002A patent/SK287296B6/sk not_active IP Right Cessation
- 2001-02-13 DK DK01907522T patent/DK1263740T3/da active
- 2001-02-13 JP JP2001560190A patent/JP4095804B2/ja not_active Expired - Fee Related
- 2001-02-13 EP EP01907522A patent/EP1263740B1/de not_active Expired - Lifetime
- 2001-02-13 CN CNB01806521XA patent/CN1179952C/zh not_active Expired - Fee Related
- 2001-02-13 HU HU0204410A patent/HU229479B1/hu not_active IP Right Cessation
- 2001-02-13 DE DE60121550T patent/DE60121550T2/de not_active Expired - Lifetime
- 2001-02-13 ES ES06075890T patent/ES2330552T3/es not_active Expired - Lifetime
- 2001-02-13 CA CA002400554A patent/CA2400554C/en not_active Expired - Fee Related
- 2001-02-13 DK DK06075890T patent/DK1686119T3/da active
- 2001-02-13 PT PT06075890T patent/PT1686119E/pt unknown
- 2001-02-13 WO PCT/EP2001/001515 patent/WO2001060805A1/en active Application Filing
- 2001-02-13 SI SI200130614T patent/SI1263740T1/sl unknown
- 2001-02-13 UA UA2002097389A patent/UA73762C2/uk unknown
- 2001-02-13 SI SI200130941T patent/SI1686119T1/sl unknown
- 2001-02-13 ES ES01907522T patent/ES2267714T3/es not_active Expired - Lifetime
- 2001-02-13 NZ NZ520752A patent/NZ520752A/en not_active IP Right Cessation
- 2001-02-14 US US09/782,930 patent/US20020103213A1/en not_active Abandoned
- 2001-02-14 AR ARP010100659A patent/AR030190A1/es not_active Application Discontinuation
- 2001-02-14 MY MYPI20010671A patent/MY135732A/en unknown
- 2001-02-14 GC GCP20011178 patent/GC0000221A/en active
- 2001-02-15 TW TW090103332A patent/TW550259B/zh not_active IP Right Cessation
- 2001-02-15 CO CO01011957A patent/CO5271661A1/es active IP Right Grant
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2002
- 2002-08-13 IL IL151236A patent/IL151236A/en not_active IP Right Cessation
- 2002-08-13 NO NO20023828A patent/NO324691B1/no not_active IP Right Cessation
- 2002-08-26 BG BG107034A patent/BG66014B1/bg unknown
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2003
- 2003-02-03 US US10/357,238 patent/US6649619B1/en not_active Expired - Lifetime
- 2003-06-09 HK HK03104052A patent/HK1053466A1/xx not_active IP Right Cessation
- 2003-10-27 US US10/694,561 patent/US7153861B2/en not_active Expired - Fee Related
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2006
- 2006-10-06 CY CY20061101441T patent/CY1105649T1/el unknown
- 2006-11-17 US US11/561,035 patent/US7470694B2/en not_active Expired - Fee Related
- 2006-11-21 US US11/561,926 patent/US7638520B2/en not_active Expired - Fee Related
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2007
- 2007-03-15 IL IL181957A patent/IL181957A0/en unknown
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2009
- 2009-01-06 US US12/349,086 patent/US7652019B2/en not_active Expired - Fee Related
- 2009-02-18 US US12/372,837 patent/US20090170877A1/en not_active Abandoned
- 2009-10-12 CY CY20091101045T patent/CY1109484T1/el unknown
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2010
- 2010-02-18 US US12/707,838 patent/US20100144765A1/en not_active Abandoned
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2011
- 2011-12-02 US US13/309,941 patent/US8871775B2/en not_active Expired - Fee Related
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2014
- 2014-10-24 US US14/522,870 patent/US9266841B2/en not_active Expired - Fee Related
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